This project will attempt to answer the questions: (1) What is the chemical nature of the toxic materials in cotton dust? (2) What are the effects of these toxic materials on the cells of the mammalian lung? (3) What relationship do these effects have to chronic disease in cotton textile workers? and (4) How might these materials be removed from cotton trash? Also this approach may be useful in several other diseases due to inhalation of dusts of vegetable origin. Such dusts contain both the natural products of the plant in question and productS of fungal and bacterial metabolism. We will use simple in vitro cell systems including leukocytes in chemotaxis chambers, explaints of ciliated respiratory epithelium, and fibroblast cultures to appraise the cell recruiting potential, capacity to increase mucous secretion or stop ciliary beating, and the alteration in fibroblast growth patterns of crude extracts, fractions and purified products of stored cotton and its major parasites. Appraisal of the responses of three of the important cell types of lung should be useful in predicting how the total organ will respond to a noxious material. We will extend the studies in vitro to experimental pathology in animals of the key positive as well as negative control materials to determine how good are the predictions made by in vitro models and what relationships these have to chronic changes produced at the organ level. We then should be able to manipulate the systems to determine how detoxification or removal might best be performed. This will require cooperation with a number of collaborators working in other areas of the problem particularly including the chemical isolation components and the processing of fibers.